Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

Soft Tissues: Alveolar rhabdomyosarcoma with t(1;13)(p36;q14) PAX7/FOXO1

Written2010-07Frederic G Barr
Department of Pathology, Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

(Note : for Links provided by Atlas : click)


ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 8920/3 Alveolar rhabdomyosarcoma
Atlas_Id 5012
Phylum Soft Tissues::Alveolar rhabdomyosarcoma
WHO/OMS Classification Soft Tissues
TUMOUR:::AlvRhabdomyosarcID5194.txt ==> 5194 TUMOUR:::AlvRhabdomyosarcID5194.txtTUMOUR:::EmbryoRhabdomyoID5193.txt ==> 5193 TUMOUR:::EmbryoRhabdomyoID5193.txt

Clinics and Pathology

TUMOUR:::t213q35q14AlvRhabdoID5013.txt ==> 5013 TUMOUR:::t213q35q14AlvRhabdoID5013.txt
Phenotype / cell stem origin Generally found in alveolar rhabdomyosarcoma (ARMS); also found in rare cases diagnosed as embryonal rhabdomyosarcoma (ERMS).
Epidemiology Occurs in ~20% ARMS cases and <5% of ERMS cases: patients tend to be younger children compared to those with t(2;13)-positive ARMS tumors.
Clinics Tumors tend to show lower invasiveness compared to those with t(2;13)-positive ARMS tumors. In metastatic cases, there is a low incidence of bone marrow involvement.
Prognosis In one study, patients with localized t(2;13) and t(1;13)-positive ARMS had comparable outcomes whereas a recent study with small numbers suggested that localized t(1;13) tumors had a better outcome than those with localized t(2;13) tumors. Among patients presenting with metastatic disease, those with t(1;13)-positive tumors had a significantly better outcome than those with t(2;13)-positive tumors. Note: these studies are based on molecular detection of the translocations.


Though a balanced 1;13 is sometimes visible in cases with the associated molecular fusion event, in many cases the balanced translocation is not visible. Instead the molecular fusion is found associated with a subsequent amplification event, usually double minute chromosomes.
Diagram of t(1;13)(p36;q14) chromosomal translocation.
Cytogenetics Molecular The product of the 1;13 translocation is amplified in ~90% of t(1;13)-positive cases. Amplification events involving 2p24 and 13q31 (as determined by DNA-based array studies).
GENE:::GC_PAX7.txt ==> 68 GENE:::GC_PAX7.txt

Genes involved and Proteins

Gene NamePAX7 (paired box 7)
Location 1p36.13
Protein Transcription factor - paired box (PAX) family.

GENE:::FOXO1ID83ch13q14.txt ==> 83 GENE:::FOXO1ID83ch13q14.txt
Gene NameFOXO1 (Forkhead box O1)
Location 13q14.11
Protein Transcription factor - forkhead box (FOX) family.

Result of the chromosomal anomaly

Hybrid Gene
Description The 1;13 translocation breaks within intron 7 of the PAX7 gene and intron 1 of the FOXO1 gene on chromosome 13 to generate a PAX7-FOXO1 fusion gene as well as a reciprocal FOXO1-PAX7 fusion gene. In ~55% of PAX7-FOXO1-positive ARMS tumors, this FOXO1-PAX3 gene is not detectable. In cases with fusion gene amplification, the PAX7-FOXO1 fusion gene is amplified whereas the reciprocal FOXO1-PAX7 fusion gene is not.
Transcript The PAX7-FOXO1 fusion transcript consists of the first 7 exons of PAX3 fused to FOXO1 exons 2 and 3. There is evidence that the PAX7-FOXO1 fusion transcript is upregulated relative to the wild-type PAX7 transcript, presumably due to increased copy number of the fusion gene by amplification.
Fusion Protein
Description The fusion gene has a 2484 nt open reading frame encoding an 828 amino acid fusion protein. This fusion protein is a transcription factor with a PAX7 DNA binding domain and FOXO1 transactivation domain.
Expression Localisation Nuclear.
Oncogenesis Transcription dysregulation. At the cellular level there is evidence of alterations in control of growth. In conjunction with other genetic changes, recipient cells show transformation in culture and tumorigenesis in injected mice.


Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?
Anderson J, Gordon T, McManus A, Mapp T, Gould S, Kelsey A, McDowell H, Pinkerton R, Shipley J, Pritchard-Jones K; UK Children's Cancer Study Group (UKCCSG) and the UK Cancer Cytogenetics Group.
Br J Cancer. 2001 Sep 14;85(6):831-5.
PMID 11556833
Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.
Barr FG, Duan F, Smith LM, Gustafson D, Pitts M, Hammond S, Gastier-Foster JM.
Genes Chromosomes Cancer. 2009 Aug;48(8):661-72.
PMID 19422036
In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusion genes in alveolar rhabdomyosarcoma.
Barr FG, Nauta LE, Davis RJ, Schafer BW, Nycum LM, Biegel JA.
Hum Mol Genet. 1996 Jan;5(1):15-21.
PMID 8789435
Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a report from the Children's Oncology Group.
Barr FG, Smith LM, Lynch JC, Strzelecki D, Parham DM, Qualman SJ, Breitfeld PP.
J Mol Diagn. 2006 May;8(2):202-8.
PMID 16645206
A consensus polymerase chain reaction-oligonucleotide hybridization approach for the detection of chromosomal translocations in pediatric bone and soft tissue sarcomas.
Barr FG, Xiong QB, Kelly K.
Am J Clin Pathol. 1995 Dec;104(6):627-33.
PMID 8526204
Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma.
Barr FG.
Oncogene. 2001 Sep 10;20(40):5736-46. (REVIEW)
PMID 11607823
PAX3 and PAX7 exhibit conserved cis-acting transcription repression domains and utilize a common gain of function mechanism in alveolar rhabdomyosarcoma.
Bennicelli JL, Advani S, Schafer BW, Barr FG.
Oncogene. 1999 Jul 29;18(30):4348-56.
PMID 10439042
Chromosomal translocation t(1;13)(p36;q14) in a case of rhabdomyosarcoma.
Biegel JA, Meek RS, Parmiter AH, Conard K, Emanuel BS.
Genes Chromosomes Cancer. 1991 Nov;3(6):483-4.
PMID 1663783
The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions.
Buckingham M, Relaix F.
Annu Rev Cell Dev Biol. 2007;23:645-73. (REVIEW)
PMID 17506689
Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group.
Davicioni E, Anderson MJ, Finckenstein FG, Lynch JC, Qualman SJ, Shimada H, Schofield DE, Buckley JD, Meyer WH, Sorensen PH, Triche TJ.
Am J Pathol. 2009 Feb;174(2):550-64. Epub 2009 Jan 15.
PMID 19147825
Fusion genes resulting from alternative chromosomal translocations are overexpressed by gene-specific mechanisms in alveolar rhabdomyosarcoma.
Davis RJ, Barr FG.
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8047-51.
PMID 9223312
Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma.
Davis RJ, D'Cruz CM, Lovell MA, Biegel JA, Barr FG.
Cancer Res. 1994 Jun 1;54(11):2869-72.
PMID 8187070
Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma.
Douglass EC, Rowe ST, Valentine M, Parham DM, Berkow R, Bowman WP, Maurer HM.
Genes Chromosomes Cancer. 1991 Nov;3(6):480-2.
PMID 1777415
Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma.
Du S, Lawrence EJ, Strzelecki D, Rajput P, Xia SJ, Gottesman DM, Barr FG.
Int J Cancer. 2005 May 20;115(1):85-92.
PMID 15688409
Structural analysis of PAX7 rearrangements in alveolar rhabdomyosarcoma.
Fitzgerald JC, Scherr AM, Barr FG.
Cancer Genet Cytogenet. 2000 Feb;117(1):37-40.
PMID 10700864
Concomitant amplification and expression of PAX7-FKHR and MYCN in a human rhabdomyosarcoma cell line carrying a cryptic t(1;13)(p36;q14).
Frascella E, Lenzini E, Schafer BW, Brecevic L, Dorigo E, Toffolatti L, Nanni P, De Giovanni C, Rosolen A.
Cancer Genet Cytogenet. 2000 Sep;121(2):139-45.
PMID 11063797
Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer Cytogenetics Group Study.
Gordon T, McManus A, Anderson J, Min T, Swansbury J, Pritchard-Jones K, Shipley J; United kingdom Children's Cancer Study Group; United Kingdom Cancer Cytogenetics Group.
Med Pediatr Oncol. 2001 Feb;36(2):259-67.
PMID 11452933
Clinical aspects of alveolar rhabdomyosarcoma with translocation t(1;13)(p36;q14) and hypotetraploidy.
Gunawan B, Fuzesi L, Granzen B, Keller U, Mertens R, Steinau G, Schumpelick V.
Pathol Oncol Res. 1999;5(3):211-3. (REVIEW)
PMID 10491019
The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system.
Jostes B, Walther C, Gruss P.
Mech Dev. 1990 Dec;33(1):27-37.
PMID 1982921
Pax3-fkhr and pax7-fkhr fusion genes impact outcome of alveolar rhabdomyosarcoma in children.
Kazanowska B, Reich A, Stegmaier S, Bekassy AN, Leuschner I, Chybicka A, Koscielniak E.
Fetal Pediatr Pathol. 2007 Jan-Feb;26(1):17-31.
PMID 17613043
Chromosomal translocation (1:13) in a case of alveolar rhabdomyosarcoma.
Kenet G, Sharon N, Rosner E, Toren A, Neumann Y, Mandel M, Kaplinsky C, Gipsh N, Berman S, Rechavi G.
J Pediatr Hematol Oncol. 1998 Jan-Feb;20(1):86-7.
PMID 9482420
Rhabdomyosarcoma: molecular diagnostics of patients classified by morphology and immunohistochemistry with emphasis on bone marrow and purged peripheral blood progenitor cells involvement.
Krskova L, Mrhalova M, Sumerauer D, Kodet R.
Virchows Arch. 2006 Apr;448(4):449-58. Epub 2005 Dec 20.
PMID 16365729
Fusions involving PAX and FOX genes in the molecular pathogenesis of alveolar rhabdomyosarcoma: recent advances.
Mercado GE, Barr FG.
Curr Mol Med. 2007 Feb;7(1):47-61. (REVIEW)
PMID 17311532
Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma.
Nishio J, Althof PA, Bailey JM, Zhou M, Neff JR, Barr FG, Parham DM, Teot L, Qualman SJ, Bridge JA.
Lab Invest. 2006 Jun;86(6):547-56.
PMID 16607381
Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.
Parham DM, Qualman SJ, Teot L, Barr FG, Morotti R, Sorensen PH, Triche TJ, Meyer WH; Soft Tissue Sarcoma Committee of the Children's Oncology Group.
Am J Surg Pathol. 2007 Jun;31(6):895-901.
PMID 17527077
Mouse mesenchymal stem cells expressing PAX-FKHR form alveolar rhabdomyosarcomas by cooperating with secondary mutations.
Ren YX, Finckenstein FG, Abdueva DA, Shahbazian V, Chung B, Weinberg KI, Triche TJ, Shimada H, Anderson MJ.
Cancer Res. 2008 Aug 15;68(16):6587-97.
PMID 18701482
PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group.
Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG.
J Clin Oncol. 2002 Jun 1;20(11):2672-9.
PMID 12039929
Cytogenetic studies in subgroups of rhabdomyosarcoma.
Whang-Peng J, Knutsen T, Theil K, Horowitz ME, Triche T.
Genes Chromosomes Cancer. 1992 Nov;5(4):299-310.
PMID 1283318


This paper should be referenced as such :
Barr, FG
Soft tissue tumors: t(1;13)(p36;q14) in alveolar rhabdomyosarcoma
Atlas Genet Cytogenet Oncol Haematol. 2011;15(4):378-380.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(1;13)(p36;q14) PAX7/FOXO1

External links

Mitelman database t(1;13)(p36;q14) [CaseList]     t(1;13)(p36;q14) [Transloc - MCList]   PAX7/FOXO1 Fusion - MCList]
COSMIC[ PAX7 ]   [ FOXO1 ]
arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionPAX7 (1p36.13) FOXO1 (13q14.11)    [fusion287] [fusion288] [fusion344]
Mitelman databasePAX7/FOXO1[MCList]    PAX7 (1p36.13) FOXO1 (13q14.11)   
Mitelman databasePAX7/FOXO1[MCList]    PAX7 (1p36.13) FOXO1 (13q14.11)   t(1;13)(p36;q14)
Disease databaseSoft Tissues: Alveolar rhabdomyosarcoma with t(1;13)(p36;q14) PAX7/FOXO1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 28 17:44:26 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us